Early microbial intervention reshapes phenotypes of newborn Bos taurus through metabolic regulations

Abstract Background The rumen of neonatal calves has limited functionality, and establishing intestinal microbiota may play a crucial role in their health and performance. Thus, we aim to explore the temporal colonization of the gut microbiome and the benefits of early microbial transplantation (MT) in newborn calves. Results We followed 36 newborn calves for 2 months and found that the composition and ecological interactions of their gut microbiomes likely reached maturity 1 month after birth. Temporal changes in the gut microbiome of newborn calves are widely associated with changes in their physiological statuses, such as growth and fiber digestion. Importantly, we observed that MT reshapes the gut microbiome of newborns by altering the abundance and interaction of Bacteroides species, as well as amino acid pathways, such as arginine biosynthesis. Two-year follow-up of those calves further showed that MT improves their later milk production. Notably, MT improves fiber digestion and antioxidant capacity of newborns while reducing diarrhea. MT also contributes to significant changes in the metabolomic landscape, and with putative causal mediation analysis, we suggest that altered gut microbial composition in newborns may influence physiological status through microbial-derived metabolites. Conclusions Our study provides a metagenomic and metabolomic atlas of the temporal development of the gut microbiome in newborn calves. MT can alter the gut microbiome of newborns, leading to improved physiological status and later milk production. The data may help develop strategies to manipulate the gut microbiota during early life, which may be relevant to the health and production of newborn calves.

L366. 79 species, 185 pathways were identified in the associations.Is there any difference for these species and pathways among the groups?Is there any trend or distribution in these species and pathways?More analysis is need.The present results contributed to limited novel insights for understanding the relationship between gut microbiota and host phenotype.L405.The results showed that the metabolites at day 35 was different from that at day 56.However, this result is different from the observed results in gut microbiota.Why?The font size in figures 3, 5 and 6 is too small.

Methods
Are the methods appropriate to the aims of the study, are they well described, and are necessary controls included?Choose an item.

Conclusions
Are the conclusions adequately supported by the data shown?Choose an item.

Reporting Standards
Does the manuscript adhere to the journal's guidelines on minimum standards of reporting?Choose an item.

Statistics
Are you able to assess all statistics in the manuscript, including the appropriateness of statistical tests used?Choose an item.

Quality of Written English
Please indicate the quality of language in the manuscript: Choose an item.

Declaration of Competing Interests
Please complete a declaration of competing interests, considering the following questions: • Have you in the past five years received reimbursements, fees, funding, or salary from an organisation that may in any way gain or lose financially from the publication of this manuscript, either now or in the future?
• Do you hold any stocks or shares in an organisation that may in any way gain or lose financially from the publication of this manuscript, either now or in the future?
• Do you hold or are you currently applying for any patents relating to the content of the manuscript?
• Have you received reimbursements, fees, funding, or salary from an organization that holds or has applied for patents relating to the content of the manuscript?
• Do you have any other financial competing interests?
• Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below.If your reply is yes to any, please give details below.
I declare that I have no competing interests I agree to the open peer review policy of the journal.I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses.I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/).I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.
Choose an item.
To further support our reviewers, we have joined with Publons, where you can gain additional credit to further highlight your hard work (see: https://publons.com/journal/530/gigascience).On publication of this paper, your review will be automatically added to Publons, you can then choose whether or not to claim your Publons credit.I understand this statement.
Yes Choose an item.